The MRL Mitochondrial Genome Decreases Murine Muscular Dystrophy Severity

It is well known that muscular dystrophy disease severity controlled by genetic modifiers. The expectation identifying these modifiers, we can illuminate additional therapeutic targets with which to combat the disease. To this end have been investigating MRL mouse strain, highly resistant dystrophy-mediated fibrosis. strain contains two mitochondrial-encoded, naturally occurring heteroplasmies: T3900C in tRNA-Met, and variable adenine insertions at 9821 tRNA-Arg. Heteroplasmies are mitochondrial mutations variably present a cell’s mitochondria. Therefore, cells contain 0 100% of each mutation. We chosen severely affected ϒ-sarcoglycan (Sgcg–/–) deficient mice on DBA2/J background as our model demonstrate effects heteroplasmies severity. Mice from (D) wildtype (M) strains were crossed for more than 10 generations establish separate, pure breeding lines: Sgcg+/–NucDMito%M Sgcg+/–NucMMito%M. Sgcg–/– separate lines analyzed 8 weeks old membrane permeability, hydroxyproline content, pAMPK fibronectin percentage heteroplasmy. identified mutation confers portion fibrosis resistance strain. These results extended significantly correlate increased mitochondria decreased beneficial mechanisms will be discussed. establishing metabolic aspects pathogenesis. pathways now investigated targets.